Transcript Prion

5
Bunyaviruses
Arenaviruses
Prion
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Bunyaviridae (C64, p651)
There are at least 200 viruses in 5 genera. Most are arboviruses and
few are rodent born viruses (hantaviruses). They cause encephalitis,
hemorrhage fever, and pulmonary syndrome (Table 1).
Table 64-1. Notable Bunyaviridae Genera
Genus
Members
Bunyavirus
Bunyamwera virus, California
encephalitis virus, La Crosse
virus, Oropouche virus; 150
members
Phlebovirus
Insect
Vector
Pathologic Conditions
Vertebrate Hosts
Mosquito
Febrile illness, encephalitis,
febrile rash
Rodents, small
mammals, primates,
marsupials, birds
Rift Valley fever virus, sandfly
fever virus; 36 members
Fly
Sandfly fever, hemorrhagic
fever, encephalitis,
conjunctivitis, myositis
Sheep, cattle,
domestic animals
Nairovirus
Crimean-Congo hemorrhagic
fever virus; 6 members
Tick
Hemorrhagic fever
Hares, cattle, goats,
seabirds
Uukuvirus
Uukuniemi virus; 7 members
Tick
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Birds
Hantavirus
Hantaan virus
None
Hemorrhagic fever with renal
syndrome, adult respiratory
distress syndrome
Rodents
Sin Nombre
None
Hantavirus pulmonary
Deer mouse
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1. Structure
l segmented –ssRNA (S, M, L) (Table 2)
l capsid
l envelope
Table 64-2. Genome and Proteins of California Encephalitis Virus
Genome*
Proteins
L
RNA polymerase, 170 kDa
M
Spike glycoprotein, 75 kDa
Spike glycoprotein, 65 kDa
Nonstructural protein, 15-17 kDa
S
Nucleocapsid protein, 25 kDa
Nucleocapsid protein, 10 kDa
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2. Replication
l virus enters cells via G1 glycoprotein and receptor-mediated endocytosis.
l Virus are assembled by budding into the Golgi apparatus and are released
by cell lysis and exocytosis.
3. Most viruses in bunyavirus genus are not in Taiwan.
l Most members of bunyavirus genus are arboviruses (transmitted by arthropod)
and cause encephalitis and hemorrhagic fever in a way very similar to
togaviruses and flaviviruses.
BOX 64-2. Disease Mechanisms for Bunyaviruses
•Virus is acquired from an arthropod bite (e.g., mosquito)
•Initial viremia may cause flulike symptoms.
•Establishment of secondary viremia may allow virus access to specific target
tissues, including the central nervous system, organs, and vascular endothelium.
•Antibody is important in controlling viremia; interferon and cell-mediated immunity
may prevent the outgrowth of infection.
4. Hantavirus
l Hantaan virus was first isolated from mice around Hantaan River of Korea in 1976.
It causes Hantaan hemorrhagic disease (fever, hemorrhage, kidney failure, shock,
and death)
l Sin Nombre virus is isolated from grand canon of US in 1993.
It causes hantavirus pulmonary syndrome. (fever, muscle ache,
interstitial pulmonary edema, respiratory failure, and death).
l Virus is transmitted by secretion of rodent like deer mice.
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5. Lab. diagnosis: It can be confirmed by serological tests and RT- PCR.
6. Treatment: There is no specific therapy or vaccine (except for Rift Valley
fever). Arthropod or rodent controls for prevention.
Arenaviruses associated with human disease (c64, p654)
Virus
Disease
Distribution
Lassa
Lassa fever
West Africa
Junin
Argentine hemorrhagic fever
South America
Sabia
Brazilian hemorrhagic fever
South America
LCMV
meningitis
Worldwide
LCMV: lymphocytic choriomeningitis virus
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Virions appear sandy because of ribosome.
Enveloped virion with 2 single strand RNA
circles (L and S).
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Transmission (zoonoses)
Rodent-to-human:
1. Inhalation of aerosolized virus
2. Ingestion of food or materials contaminated by infected rodent excretion.
3. Catching and preparing mice as a food source
Human-to-human:
1. Direct contact with blood, tissues, secretions or excretions of infected humans
2. Needle stick or cut
3. Inhalation of aerosolized virus
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Epidemiology and clinical syndromes
1. LCM
• There are 5 to 20% mice have LCMV in US.
• LCM is characterized by fever and meningeal illness. About
10% patients have CNS syndromes.
• LCM is usually not fatal. In general, mortality is less than 1%.
• Avoid contact with mice and pet hamsters.
2. Lassa and other hemorrhagic fever
Clinical illness is characterized by fever, coagulopathy, petechia,
hemorrhage, and shock. Death occurs in about 50% of Lassa
fever cases.
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Laboratory diagnosis
--Infection can be detected by serology and RT-PCR.
--If the case is suspected, laboratory personnel should be warned.
Specimens should processed in BSL 3 (LCM) or 4 (Lassa and others)
facilities.
Treatment
--Ribavirin is used to treat Lassa fever.
--Supportive measures
Prevention and control of outbreak by limiting contact with rodents.
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Unconventional slow viruses: Prions (C67, p691)
Prion :Proteinaceous infectious particle
1.causes spongiform encephaolpathies
observed in hosts
2. Characteristics of diseases
--long incubation periods (30 years)
before developing clinical illness
BOX 67-1. Slow Virus Diseases
Human
•Kuru
•Creutzfeldt-Jakob disease (CJD)
•Gerstmann-Sträussler-Scheinker (GSS syndrome)
•Fatal familial insomnia (FFI)
Animal
•Scrapie (sheep and goats)
•Transmissible mink encephalopathy
•Bovine spongiform encephalopathy (BSE; mad cow disease)
•Chronic wasting disease (mule, deer, and elk)
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3. Comparison of Classic Viruses and Prions
Filterable, infectious agents
Yes
Yes
Presence of nucleic acid
Yes
No
Defined morphology (electron microscopy)
Yes
No
Presence of protein
Yes
Yes
Formaldehyde
Yes
No
Proteases
Some
No
Heat (80°C)
Most
No
Ionizing and ultraviolet radiation
Yes
No
Disinfection by:
Disease
Cytopathologic effect
Yes
No
Incubation period
Depends on virus
Long
Immune response
Yes
No
Interferon production
Yes
No
Inflammatory response
Yes
No
Table 67-2. Comparison of
Scrapie Prion Protein (PrPSc) and (Normal) Cellular Prion Protein (PrPC)
Structure
PrPSc
PrPC
Globular
Extended
Protease resistance Yes
No
Presence in scrapie Yes
fibrils
No
Location in or on
cells
Cytoplasmic vesicles and
extracellular milieu
Plasma
membrane
Turnover
Days
Hours
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4. Scrapie :
b. model for proliferation of prion
Death (vacuolation) of neurons
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5. Pathogenesis and immunity
BOX 67-2. Pathogenic Characteristics of Slow Viruses
No cytopathologic effect in vitro
Long doubling time of at least 5.2 days
Long incubation period
Cause vacuolation of neurons (spongiform), amyloid-like plaques, gliosis
Symptoms that include loss of muscle control, shivering, tremors, dementia
Lack of antigenicity
Lack of inflammation
Lack of immune response
Lack of interferon production
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6. Epidemiology
-- CJD is transmitted by injection, transplantation of contaminated
tissues (corneas), contact with contaminated medical device
(brain electrode), and food.
-- CJD, GSS, and FFI are also inheritable.
-- Kuru is due to the eating of dead body.
-- variant form CJD (vCJD) in younger people
(<45 years old) in UK after
mad cow disease in 1980.
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Kuru: shivering or trembling
in Fore tribe of New Guinea , who used to eat dead human body.
Women and children are high risk.
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7. Clinical syndromes:
--Spongiform encephalopathies are characterized by a loss of muscle
control, shivering, myoclonic jerks, tremors, loss of coordination,
dementia, and death.
8. Lab. diagnosis: Western blot for tonsil biopsy and histology for autopsy.
9. Treatment, prevention, and control
-- Rigorous disinfection by autoclaving at 15 psi for 1 hour instead of
20 minutes and treatment with 5% HCl, and 1 M NaOH
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BOX 67-4. Clinical Summaries
CJD: A 63-year-old man complained of poor memory and difficulty with
vision and muscle coordination. Over the course of the next year, he
developed senile dementia and irregular jerking movements, progressively
lost muscle function, and then died.
VCJD: A 25-year-old is seen by a psychiatrist for anxiety and depression.
After 2 months, he has problems with balance and muscle control and has
difficulty remembering. He develops myoclonus and dies within 12 months
of onset.
Case study and questions:
A 70-year-old woman complained of severe headaches and appeared dull and apathetic
with a constant tremor in the right hand. One month later, she suffered memory loss and
moments of confusion. The patient’s condition continued to deteriorate, and an abnormal
electroencephalograph tracing showing periodic biphasic and triphasic slow-wave
complexes was obtained 2 months later onset of symptoms. By 3 months, the patient was in
a comalike state. She also had occasional spontaneous clonic twitching of the arms and legs
and a startle myoclonic jerking response to a loud noise. The patient died of pneumonia 4
months after the onset of symptoms. No gross abnormalities were noted at autopsy.
Astrocytic gliosis of the cerebral cortex with fibrils and intracellular vacuolation
throughout the cerebral cortex were seen on microscopic examination. There was no
swelling and no inflammation.
1. What viral neurological diseases would have been considered in the differential
diagnosis formulated on the basis of the symptoms described? What other diseases?
2. What key features of the postmortem findings were characteristic of the disease caused
by unconventional slow virus agents (spongiform encephalopathies, prions)?
3. What key features distinguish the unconventional slow virus diseases from more
conventional neurological viral diseases?
4. What precautions should the pathologist have taken for protection against infection
during the postmortem examination?
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